The malaria merozoite and the infected erythrocyte express ligands on the cell surface that bind host cell receptors. We have identified the parasite domain, the Duffy binding like (DBL), on P. falciparum, P. vivax, and P. knowlesi that bind human and rhesus erythrocytes. The DBL domain is found in var genes involved in antigenic variation and are thought to be involved in binding to host cells. These parasite ligands are important in the pathogenesis of disease: invasion of erythrocytes, antigenic variation, cytoadherence to escape spleen killing, and cerebral malaria. We are determining the importance of var genes in rosetting that correlates with disease and the receptor on erythrocytes for the binding. We are also determining their role at the molecular level in binding to ICAM1, an endothelial receptor whose expression is upregulated in cerebral endothelium during cerebral malaria. The merozoite ligands for binding to glycophorin A-independent pathways for erythrocyte invasion are under study.